Abstract
9566 Background: Beta glucans are complex, naturally occurring polysaccharides that prime leucocyte dectin and CR3 receptors. Based on our preclinical observations that oral barley-derived (1→3,1→4)-β-D-Glucan (BG) synergizes with the murine anti-GD2 antibody 3F8 against neuroblastoma (NB) (Clin Cancer Res 8:1217), we conducted a phase I study to determine the safety of the combination of BG and 3F8 in patients with resistant NB. Methods: Heavily pre-treated patients with recurrent or refractory advanced stage NB were treated with 3F8/BG. Each cycle consisted of intravenous (IV) 3F8 at a fixed dose of 10 mg/m2/day ×10 days, plus oral BG dose escalated from 10 to 80 mg/kg/day ×10 days in 4 cohorts of 6 patients each. Patients without human anti-mouse antibody (HAMA) could be re-treated up to a total of 4 cycles. Results: Twenty-three patients with stage 4 and one with stage 3 NB (M:F = 11:13; median age 8 (range 2–19) years completed 47 cycles of therapy with 3F8/BG. 8 patients had progressive disease (PD) while 16 had stable refractory NB (SD) at enrollment. All patients completed at least one cycle of therapy and were evaluated for toxicity and response. Maximum tolerated dose for BG was not reached. Two patients developed dose-limiting toxicities (DLT). Both had grade 4 thrombocytopenia after completing one cycle of treatment: one at BG dose of 20mg/kg/day and the other at 40 mg/kg/day. Both cases responded to therapy with a short course of ITP (idiopathic thrombocytopenic purpura) therapy; one subsequently developed chronic ITP. There were no other >grade 2 toxicities related to 3F8/BG therapy. 14, 4, 2 and 6 patients completed 1, 2, 3 and 4 cycles respectively. Reasons for withdrawal in patients who did not complete 4 cycles were PD in 10, persistently elevated HAMA in 6 and DLT in 2. Overall 11 patients had SD and 13 PD. 14/23 patients with positive MIBG scans prior to therapy demonstrated improvement after one cycle. Responses did not correlate with BG dose received. 7 patients, all with residual disease survive at a median of 40 (range 24–45) months post-treatment. Conclusions: 3F8/BG is well tolerated and shows activity against resistant NB. Further clinical investigation of this novel combination is warranted. No significant financial relationships to disclose.
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